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Abstract
Background and Objectives Serum antioxidant vitamins and carotenoids may protect against neurodegeneration with age. We examined associations of these nutritional biomarkers with incident all-cause and Alzheimer disease (AD) dementia among US middle-aged and older adults.
Methods Using data from the third National Health and Nutrition Examination Surveys (1988–1994), linked with Centers for Medicare & Medicaid follow-up data, we tested associations and interactions of serum vitamins A, C, and E and total and individual serum carotenoids and interactions with incident AD and all-cause dementia. Cox proportional hazards regression models were conducted.
Results After ≤26 years follow-up (mean 16–17 years, 7,283 participants aged 45–90 years at baseline), serum lutein+zeaxanthin was associated with reduced risk of all-cause dementia (65+ age group), even in the lifestyle-adjusted model (per SD: hazard ratio [HR] 0.93, 95% CI 0.87–0.99; p = 0.037), but attenuated in comparison with a socioeconomic status (SES)–adjusted model (HR 0.92, 95% CI 0.86–0.93; p = 0.013). An inverse relationship was detected between serum β-cryptoxanthin (per SD increase) and all-cause dementia (45+ and 65+) for age- and sex-adjusted models (HR 0.86, 95% CI 0.80–0.93; p < 0.001 for 45+; HR 0.86, 95% CI 0.80–0.93; p = 0.001 for 65+), a relationship remaining strong in SES-adjusted models (HR 0.89, 95% CI 0.82–0.96; p = 0.006 for 45+; HR 0.88, 95% CI 0.81–0.96; p = 0.007 for 65+), but attenuated in subsequent models. Antagonistic interactions indicate putative protective effects of 1 carotenoid may be observed at lower levels other carotenoids or antioxidant vitamin.
Discussion Incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and β-cryptoxanthin levels. Further studies with time-dependent exposures and randomized trials are needed to test neuroprotective effects of supplementing the diet with select carotenoids.
Classification of Evidence This study provides Class II evidence that incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and β-cryptoxanthin levels.
Glossary
- 1995 HEI=
- Healthy Eating Index, 1995 version;
- AD=
- Alzheimer disease;
- BMI=
- body mass index;
- CMS=
- Centers for Medicare & Medicaid Services;
- CPT4=
- Common Procedural Terminology;
- DHA=
- docosahexaenoic acid;
- HMO=
- Health Maintenance Organization;
- HR=
- hazard ratio;
- ICD-9=
- International Classification of Diseases, 9th revision;
- ICD-10=
- International Classification of Diseases, 10th revision;
- IRB=
- institutional review board;
- MAR=
- mean adequacy ratio;
- MEC=
- mobile examination center;
- NDI=
- National Death Index;
- NH=
- Non-Hispanic;
- NHANES III=
- Third National Health and Nutrition Examination Survey;
- PIR=
- poverty income ratio;
- ROS=
- reactive oxygen species;
- SES=
- socioeconomic status
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD.
Editorial, page 871
Class of Evidence: NPub.org/coe
- Received September 29, 2021.
- Accepted in final form February 10, 2022.
- © 2022 American Academy of Neurology
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